No abstract

Antibody-based therapeutics are effective against conditions ranging from acute infections to malignancy. They may prove crucial in combating bioterrorism and responding to drug-resistant and emerging pathogens. At present the cost of producing therapeutic monoclonal antibodies is between $1,000 to $6,000 per gram. The need to administer antibodies parenterally at frequent intervals further drives the cost of this treatment. Here we present an antibody delivery system, termed paratransgenesis, with the potential to overcome these limitations. The paratransgenic approach involves genetically transforming a commensal or symbiont bacterium to express foreign molecules that target pathogens. We describe transformation of Corynebacterium pseudodiptheriticum, a commensal bacterium found in the human respiratory tract, to express a murine single-chain antibody binding progesterone. The antibody was functional and bound specifically to progesterone in a concentration-dependent manner. This marker antibody system is the precursor to development of expression systems producing recombinant humanized single-chain antibodies. Studies are in progress evaluating fitness, transgene stablility, and pathogenecity of the genetically engineered C. pseudodiptheriticum. We anticipate developing a repertoire of expressed molecules targeting infectious agents and surface epitopes of pulmonary mass lesions. If expression systems for anti-pathogen molecules in C. pseudodiptheriticum and other respiratory commensal bacteria can be optimized, these bacteria have the potential for a range of therapeutic and prophylactic applications.

No abstract

Public reporting burden for this collection o* information n estimated to average I hoof per response, including the time for reviewing instructions, searching emitting date sources, gathering trA maintaining the data needed, and completing and reviewing the collection of information Send comments regarding this burden estimate oc any other aspect of this collection of Information, including suggestions for reducing this burden, to Washington Headquarters Services. Directorate for information operations tnd Reports, \2 u Jefferson Oavit Highway. Suit« 1204. Arlington. VA ]H0i-*}02. and to the Office of Management and Budget. Paperwork Reduction Project (0704-0188). Washington. DC 20503. AGENCY USE ONLY (Leave blink)2. REPORT DATE 29 December 1995 REPORT TYPE ANO DATES COVEREDTechnical, 7/94 -12/94 TITLE AND SUBTITLEA Two-Stage Littoral Warfare Ship System Design AUTHOR(S)Prof. C. N. Calvano, LCDR G. Blaylock, LT R. Burger, LT E. Hoy, LT R. Thiel, LT D. Wagnon, LT C. Vejvoda S. FUNDING NUMBERS PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)Naval Postgraduate School Monterey, CA 93943 PERFORMING ORGANIZATION REPORT NUMBERfiPS-ME-95-005 SPONSORING /MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSORING/MONITORING AGENCY REPORT NUMBER SUPPLEMENTARY NOTESThe views expressed in this report are those of the authors and do not reflect the official policy or position of the Department of Defense or the U.S. Government. DISTRIBUTION/AVAILABILITY STATEMENTApproved for Public Distribution; Distribution Unlimited 12b. DISTRIBUTION CODE ABSTRACT (Maximum 200 words)A Systems Engineering approach to the development of a flexible warship system intended for littoral warfare is presented, followed by a description of the preliminary design of the ship shown by analysis to the most cost-effective. The requirements for the project reported were to consider the need to diversify the Navy's current blue water fleet by adding a number of affordable vessels which can be tailored to accomplish specific objectives, as deemed necessary. The ships are to provide flexible response in littoral areas, under an Aegis-ship area air defense umbrella. A "twostage" approach consisting of a "mother" ship carrying other surface and air craft was considered most effective. In this approach, the flexible, tailored nature of the response is provided by various kinds of "daughter" craft, permitting changing the loadout of the mother ship to respond to current or anticipated needs. The nature of the various daughter craft was arrived at in a previous course; this report concentrates primarily on the definition, feasibility studies and preliminary design of the "mother" ship. This report documents a systems engineering and design capstone project undertaken by students in the Total Ship Systems Engineering (TSSE) program at the Naval Postgraduate School and performed over two academic quarters. The project was under the direction of Prof. C. N. Calvano. (The officer students who comprised the design team were: LCDR Gene Blaylock; LT Robert Burger; LT E...

No abstract